The over-arching aim of this proposal is to identify an impairment in neural mechanisms involved in emotion regulation and examine its relationship to emotional distress symptoms in people's daily lives. Emotional distress symptoms are found in a range of disorders (e.g., major depression, borderline personality disorder, and anxiety disorders), in part explaining extremely high comorbidity across these disorders. These disorders can be very common (e.g., combined prevalence over 1/3 of US population), are associated with intense personal suffering, and are associated with great costs to society (e.g., depression one of the leading causes of disability; anxiety disorders double medical care costs). Emotion regulation involves attempts to influence the presence, type, experience, and expression of emotion and emotional distress psychopathology is often posited to reflect impaired emotion regulation. Converging human and animal research has identified top-down ventromedial prefrontal cortex (vmPFC) regulation of amygdala activation as a critical neural emotion regulation mechanism, with some evidence that deficits in this mechanism are related to emotional distress psychopathology. Unlike possibly all previous research that examined the functional consequences of impaired vmPFC-amygdala functional connectivity, this neural deficit will be identified with functional magnetic resonance imaging (fMRI) by using both resting state data as well two different emotion regulation task paradigms, one implicit and the other explicit. This will provide converging evidence across very different functional imaging contexts to assess the breadth of this neural deficit. However, the relationship between this neural emotion dysregulation deficit and its manifestation in people's daily lives is still unknown. Previous research suggests that key emotional distress symptoms and correlates are often inaccurately recalled. Ambulatory assessment (AA) is a powerful, innovative way to assess affective, behavioral, and physiological symptoms and correlates in real world environments reliably (e.g., with smart phones), while minimizing the inaccuracy of retrospective self-reports. The use of AA will allow accurate characterization of how impaired vmPFC-amygdala functional connectivity translates into people's daily life experiences, such as self-reported negative affect affective instability, and behavioral dysregulation. In addition, physiological assessment is a critical complement to self-reported affect in order to validly assess emotional states. The current study will use wireless and continuous physiological assessment to provide converging evidence to self-reported emotional distress symptoms. Furthermore, this study will examine the relationship between this neural emotion dysregulation endophenotype with the frequency and duration (i.e., emotional recovery time) of real world emotional distress episodes measured objectively with continuously recorded physiological activity. Understanding the specific relationship between this neural emotion dysregulation and emotional distress psychopathology will have important implications assessment and treatment.